Ototoxicity of drugs

The paper included the most current information about the mechanisms of ototoxicity of five groups of the most popular drugs: a) antibiotics, b) chemotherapeutics (cytostatic) agents, c) loop diuretics, d) salicylate and nonsteroidal anti-inflammatory drugs, as well as e) progestagen contraceptives minimized or even prevented by thoughtful selection of drug, attention to risk factors and careful patient monitoring.     

New lipid lowering drugs and new effects of old drugs

Old lipid acting drugs (fibrates, resins and niacin) continue to demonstrate morbidity and mortality benefits with variable efficacy and safety. Controlled trials have provided efficacy and safety data that support the use of statins as the first choice in the treatment and prevention of atherosclerosis. Knowledge of old and new mechanisms of action, optimal doses, pharmacokinetic behavior and drug interactions improve the safety and effectiveness of these hypolipidemic agents.     

Hemostatic drugs

Recent research has investigated drug combinations that enhance the analgesic effectiveness of their component substances. Many studies have examined the combination of opioids and psychostimulant drugs, such as amphetamine and methylphenidate. Despite the positive results reported in the literature, this combination is rarely used in clinical practice. The purpose of this paper is to review the literature on the opioid-amphetamine combination. Experiments with animal and human subjects provide convincing evidence that d-amphetamine or methylphenidate potentiate the analgesic effects of morphine. Psychostimulant drugs have been shown in animal studies to possess intrinsic analgesic properties and to have the ability to enhance the analgesic properties of opioids when both types of drugs are given in combination. Studies with human subjects have confirmed the enhancement of opioid analgesia by amphetamines and, in addition, have demonstrated that psychostimulant drugs produce a decrease in somnolence and an increase in general cognitive abilities. The greater cognitive alertness, moreover, allows the use of larger opioid doses, which can produce a substantial increase in analgesia. These results indicate another possible method to enhance the quality of life in patients with difficult pain problems. Although the enhanced cognitive effects are well established, the effects on pain need further study to determine the mechanisms of action and the drug combinations and administration patterns that would maximize their effects.     

Anti-obesity drugs

In patients with hematological malignancies invasive mycoses occur frequently. In this retrospective study autopsy and histopathology material of 171 patients with hematological malignancy who had died between 1994 and 1996 at the 1st Department of Internal Medicine (Hematology), St. László Hospital, Budapest was analysed. In cases with invasive fungal infection post mortem results were compared to clinical and microbiological data. Through the three years' period an invasive mycosis could be confirmed in 33 patients by autopsy. Aspergillosis occurred in 21, candidiasis in 11, other fungal infections in 2 cases, a double infection was seen in 1 patient. The incidence was 19.2% (in invasive candidiasis: 6.4%, in aspergillosis 12.2%). Invasive aspergillosis most frequently was seen in the lung (71%), while candidiasis occurred mainly in the intestinal tract (42%). Cultures for mycology were collected from the autopsy material of 9 patients, of which 8 gave positive results. A previous fungal colonisation results was confirmed in 23 patients, but based on colonisation conclusions rarely could be driven concerning the species causing invasive infection. Sensitivity of Aspergillus antigen and antibody tests was 45 and 50%, respectively. Predisposing factors for invasive aspergillosis and candidiasis were similar, except for duration of neutropenia (24 vs. 12 days, p < 0.004). The antifungal drug most frequently used was amphotericin B. We observed a persisting infection in invasive pulmonary aspergillosis and chronic disseminated candidiasis in spite of the administration of a cumulative dosis of 1-2 g. Most frequently Aspergillus infections--primarily that of the lung--can be seen. Presence of invasive mycoses can usually be confirmed in vivo, but an early diagnosis still remains unsolved.     

Anti-invasion drugs

Most of the pharmaceuticals in clinical practice today for treatment of breast and other cancers are cytotoxic or cytostatic inhibitors of tumor growth. While this type of drug has found its place, along with surgery and radiotherapy, in treatment of disease, the breast cancer death rate has not decreased. This appears to be the result of rising incidence, resistance to therapy, and metastasis of the disease. Since distant metastasis (usually indicated by lymph node involvement) of breast cancer is related only indirectly to tumor size, it would appear that a concerted effort should be made to discover drugs which directly interfere with this complex process. Metastasis appears to depend upon tumor cell motility, dedifferentiation, local invasion, and angiogenesis. Significant progress has been recently made in the creation of new animal models of metastasis and in identifying several new drugs which may be suitable for clinical inhibition of this process. This article reviews current findings on anti-invasion/metastasis drugs with a focus on breast cancer.     

Anti-atherogenic drugs

Rupture of an instable plaque, characterized by a large lipid-rich central core, inflammatory cells, and a thin fibrous cap, causes sudden thrombus formation and acute coronary syndromes (ACS). Lipid lowering therapy by HMG-CoA reductase inhibitors leads to reduction of cardiovascular complications, but has very small effect on the degree of stenosis of ACS. Oxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Probucol improves the restenosis rate after coronary angioplasty if given before PTCA (percutaneous transluminal coronary angioplasty). These results will provide a better understanding of drug action, help explain certain drug interactions, and facilitate the choice of a drug for ACS.     

Gastrointestinal drugs

The cutaneous glands of the forehead and the metatarsus were studied by histological and histochemical methods and electron microscopy in adult male and female impalas in various seasons of the year. All glandular areas consist of apocrine and holocrine glands, which, however, occur in different proportions. Our findings in the apocrine gland cells suggest (1) the synthesis and exocytosis of a glycoproteinaceous secretory product stored in secretory granules, (2) typical apocrine secretion of the transformed apical cytoplasm, and (3) transepithelial fluid transport. The Golgi apparatus and apical membrane have binding sites for several lectins (PNA, HPA, RCA I, WGA). Cytokeratins 7, 14 and 19 are expressed at various intracellular localizations, suggesting an active role in the secretory mechanisms. The glands of the male forehead show marked seasonal changes in activity that are correlated with the main phases of the reproductive cycle, with the highest cellular activity occurring during the rut in April/May. The female forehead glands are only moderately developed and do not undergo seasonal changes. The metatarsal glands are of equal size in males and females and show no seasonal changes in activity. This study supports the hypothesis that (1) forehead glands in the male have a signaling role in the rut and (2) the metatarsal glands have a more general, probably social role maintaining and restoring contact between herd members.     

Poisoning with anti-hypertensive drugs: beta-adrenoceptor blocker drugs

The effects of poisoning with beta-blockers may be serious, but are usually self-limiting provided adequate support is given. If there is no evidence of toxicity and the degree of overdose is small, clinical observation may be all that is required. This review examines the cases of overdosage with beta-blockers reported in the literature, the presenting symptoms and possible strategems of management for such patients.     

New drugs of 1997

OBJECTIVE: To provide information regarding the most important properties of the new therapeutic agents marketed in 1997. DATA SOURCES: Published studies, drug information reference sources, and product labeling. DATA SYNTHESIS: A record-setting number of 45 new therapeutic agents were marketed in 1997. The indications and information on dosage and administration for each new agent are reviewed, as are the most important pharmacokinetic properties, adverse events, drug interactions, and other precautions. Practical considerations for the use of the new agents are also discussed. Where possible, the properties of the new drugs are compared with those of older drugs marketed for the same indications. CONCLUSION: A number of the new therapeutic agents marketed in 1997 have important advantages over older medications. An understanding of the properties of these agents is important for the pharmacist to effectively counsel patients about their use and to serve as a valuable source of information for other health professionals regarding these drugs.     

A prospective study of drugs and pregnancy. 4. Miscellaneous drugs

The results are presented of a prospective study on drug use during pregnancy involving antibiotics, analgesic drugs and iron and vitamin preparations. The study was conducted in Malm? between 1963 and 1965. No unfavourable effect of the use of antibiotics, mainly penicillin and sulphonamides, could be demonstrated. Among 15 women who had an infant with hypospadias, three had used penicillin during the first trimester, but this may well be coincidental. Analgesic drug use shows a variability which resembles that previously described for psychopharmaca. No effect on the malformation rate or infant survival could be found. A possible lengthening of the mean duration of pregnancy occurred after the use of analgesic drugs during the 2nd or 3rd trimesters. Women who are going to have a dead or malformed infant use iron and/or vitamin preparations less often during late pregnancy than women who prove to have a normal infant. When such drugs were used, the percentage of pregnancies ending in birth before the 38th week is reduced, and the birth weight among term babies is higher. The associations between pregnancy outcome and the use of iron and vitamin preparations is probably indirect, due to social factors associated with drug use.     

New antiepileptic drugs

Survival of Escherichia coli O157:H7 strains QA 326, and ATCC 43889, 43894, and 43895 after freezing (-20 degrees C, 24 h) and thawing (4 degrees C for 12 h, 23 degrees C for 3 h, or microwave heating of 700 W for 120 s) in ground beef patties was determined by reference most probable number (MPN), hydrophobic grid membrane filter SD-39 agar, and sorbitol MacConkey agar (SMA) spread-plating methods. Populations decreased from 0.62 to 2.52 log10 CFU/g, with the extent varying significantly by strain. Strain QA 326 populations almost always decreased the most, up to 1.87 log10 CFU/g more than the least sensitive strain. Microwave heating was the most lethal thawing treatment for strain QA 326, and 4 degrees C thawing was the most lethal treatment for strain ATCC 43894. Thawing treatments varied in relative lethality for the other two strains. For strain QA 326 (4 degrees C and microwave thaw treatments) and strain ATCC 43889 (4 and 23 degrees C thawing), the enumeration method significantly affected a population decrease. The SD-39 agar method best recovered strain QA 326 while the SD-39 agar method and the reference MPN method best recovered strain ATCC 43889 after 4 and 23 degrees C thawing, respectively. The greatest difference in population decrease measured by any two methods was 0.58 log10 CFU/g. Results showed (i) a wide range in freeze-thaw sensitivity among E. coli O157:H7 strains, (ii) no thawing method had consistently and significantly greater lethality, and (iii) the reference MPN, SD-39 agar, and SMA methods differed little in ability to enumerate E. coli O157:H7.